INCREASED EXPRESSION OF TRANSFORMING GROWTH-FACTOR BETA-S AFTER ACUTEEDEMATOUS PANCREATITIS IN RATS SUGGESTS A ROLE IN PANCREATIC REPAIR

Background-Transforming growth factor beta isoforms (TGF beta s) belon g to a family of multifunctional regulators of cellular growth and dif ferentiation. They are mitogenic and chemotactic for fibroblasts and a re potent stimulators of extracellular matrix production (collagen) an d deposition. Upregulation of TGF beta transcription has been reported for several in vivo systems during repair after injury. Aims-To study the expression of the three mammalian isoforms of TGF beta (TGF beta 1-3) and their relation to collagen expression as a marker for fibrobl ast response in acute oedematous pancreatitis in rats. Methods-Using n orthern blot analysis and immunohistochemistry, the expression and loc alisation of TGF beta isoforms, collagen, and amylase were analysed du ring the course of acute oedematous pancreatitis in rats, experimental ly induced by intravenous caerulein infusion. Results-Induction of acu te pancreatitis resulted in a biphasic peak pattern of expression of T GF beta 1, beta 2, and beta 3 mRNA, with a pronounced increase from da y 1 to day 3 (sixfold, 2.5-fold, fivefold, respectively) and again fro m day 5 to day 7 (threefold, 2.3-fold, 3.5-fold, respectively). The te mporal changes in TGF beta mRNA identically paralleled the expression in collagen mRNA. In contrast, amylase mRNA expression, used as a gene ral indicator of acinar cell integrity, was slightly decreased after i nduction of acute pancreatitis. Immunohistochemical analysis of pancre atitis tissue showed that increased expression of TGF beta s was mainl y present in the pancreatic acinar and ductal cells; this was evident within one day after pancreatitis induction. Conclusion-Overexpression of TGF beta s after induction of acute pancreatitis suggests a role f or these proteins in pancreatic repair and remodelling. The increased levels of TGF beta s may help suppress immune activation, and may cont ribute to the increase in the extracellular matrix including collagen and to the repair of the pancreatic parenchyma.